age-1;daf-16

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Genetic mutants with age-1, daf-16 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Diet
HT115; OP51
Lifespan (days)
17.9
Lifespan change (compared to wild type)
-22.84%
Phenotype
Down-regulation of daf-16 in adulthood suppressed longevity of age-1(hx546) animals.
Lifespan comparisons
Double mutant age-1(hx546);daf-16(RNAi) has a lifespan of 17.9 days, while single mutant daf-16(RNAi) has a lifespan of 16.9 days, single mutant age-1(hx546) has a lifespan of 32.1 days and wild type has a lifespan of 23.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Morley JF, Morimoto RI, 2004, Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell. 15(2):657-64 14668486 Click here to select all mutants from this PubMed ID in the graph
Abstract
The correlation between longevity and stress resistance observed in long-lived mutant animals suggests that the ability to sense and respond to environmental challenges could be important for the regulation of life span. We therefore examined the role of heat shock factor (HSF-1), a master transcriptional regulator of stress-inducible gene expression and protein folding homeostasis, in the regulation of longevity. Down-regulation of hsf-1 by RNA interference suppressed longevity of mutants in an insulin-like signaling (ILS) pathway that functions in the nervous system of Caenorhabditis elegans to influence aging. hsf-1 was also required for temperature-induced dauer larvae formation in an ILS mutant. Using tissue-specific expression of wild-type or dominant negative HSF-1, we demonstrated that HSF-1 acts in multiple tissues to regulate longevity. Down-regulation of individual molecular chaperones, transcriptional targets of HSF-1, also decreased longevity of long-lived mutant but not wild-type animals. However, suppression by individual chaperones was to a lesser extent, suggesting an important role for networks of chaperones. The interaction of ILS with HSF-1 could represent an important molecular strategy to couple the regulation of longevity with an ancient genetic switch that governs the ability of cells to sense and respond to stress.

Temperature °C
20
Lifespan (days)
13.24
Lifespan change (compared to wild type)
-31.08%
Phenotype
daf-16 RNAi completely abolished the synergistic effect of drp-1 and daf-2/age-1 mutations.
Lifespan comparisons
Double mutant age-1(hx546);daf-16(RNAi) has a lifespan of 13.24 days, while single mutant daf-16(RNAi) has a lifespan of 12.65 days and wild type has a lifespan of 19.21 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Yang CC et al., 2011, The dynamin-related protein DRP-1 and the insulin signaling pathway cooperate to modulate Caenorhabditis elegans longevity. Aging Cell. 10(4):724-8 21463460 Click here to select all mutants from this PubMed ID in the graph
Abstract
Here, we report that inactivation of the Caenorhabditis elegans dynamin-related protein DRP-1, a key component responsible for mitochondrial fission and conserved from yeast to humans, dramatically enhanced the effect of reduced insulin signaling (IIS) to extend lifespan. This represents the first report of a beneficial impact of manipulating mitochondrial dynamics on animal lifespan and suggests that mitochondrial morphology and IIS cooperate to modulate aging.

Search genes: age-1 daf-16

Entrez ID
Symbol
GenAge
Wormbase ID

174762
age-1
View on GenAge (age-1)
WBGene00000090

Phosphatidylinositol 3-kinase age-1;hypothetical protein

Locus: CELE_B0334.8

Wormbase description: age-1 encodes the C. elegans ortholog of the phosphoinositide 3-kinase (PI3K) p110 catalytic subunit; AGE-1, supplied maternally and embryonically, is a central component of the C. elegans insulin-like signaling pathway, lying downstream of the DAF-2/insulin receptor and upstream of both the PDK-1 and AKT-1/AKT-2 kinases and the DAF-16 forkhead type transcription factor, whose negative regulation is the key output of the insulin signaling pathway; in accordance with its role in insulin signaling, AGE-1 activity is required for regulation of metabolism, life span, dauer formation, stress resistance, salt chemotaxis learning, fertility, and embryonic development; although the age-1 expression pattern has not yet been reported, ectopic expression studies indicate that pan-neuronal age-1 expression is sufficient to rescue life-span defects, while neuronal, intestinal, or muscle expression can partially rescue dauer formation, and neuronal or muscle expression can rescue metabolic defects.

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Orthologs of age-1;daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Pik3cd
Mus musculus	Foxo1;Pik3cd
Mus musculus	Foxo4;Pik3cd
Mus musculus	Foxo3;Pik3cd
Mus musculus	Foxo6;Pik3ca
Mus musculus	Foxo1;Pik3ca
Mus musculus	Foxo4;Pik3ca
Mus musculus	Foxo3;Pik3ca
Mus musculus	Foxo6;Pik3cb
Mus musculus	Foxo1;Pik3cb
Mus musculus	Foxo4;Pik3cb
Mus musculus	Foxo3;Pik3cb
Mus musculus	Foxo6;Pik3cg
Mus musculus	Foxo1;Pik3cg
Mus musculus	Foxo4;Pik3cg
Mus musculus	Foxo3;Pik3cg

Orthologs of age-1 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	Pi3K92E

Not in SynergyAge
Species	Gene
Mus musculus	Pik3cd
Mus musculus	Pik3ca
Mus musculus	Pik3cb
Mus musculus	Pik3cg

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3